Delayed Wound Closure in Fibromodulin-Deficient Mice Is Associated with Increased TGF-β3 Signaling

Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal skin wound repair through, in part, transforming growth factor-Β (TGF-Β) modulation. Using an adult fmod-null (fmod -/-) mouse model, this study further elucidates the interplay between FMOD and TGF-Β expression during cutaneous repair and scar formation. Full-thickness skin wounds on fmod -/- and wild-type (WT) mice were closed primarily and analyzed. Histomorphometry revealed delayed dermal cell migration leading to delayed wound closure and significantly increased scar size in fmod -/- mice relative to WT, which was partially rescued by exogenous FMOD administration. In addition, fmod -/- wounds exhibited early elevation (within 24 hours post-wounding) of type I and type II TGF-Β receptors as well as unexpectedly high fibroblast expression of TGF-Β3, a molecule with reported antifibrotic and antimigratory effects. Consistent with elevated fibroblastic TGF-Β3, fmod -/- fibroblasts were significantly less motile than WT fibroblasts. fmod -/- fibroblasts were also more susceptible to migration inhibition by TGF-Β3, leading to profound delays in dermal cell migration. Increased scarring in fmod -/- mice indicates that TGF-Β3\u27s antimotility effects predominate over its antifibrotic effects when high TGF-Β3 levels disrupt early fibroblastic wound ingress. These studies demonstrate that FMOD presence is critical for proper temporospatial coordination of wound healing events and normal TGF-Β bioactivity. © 2011 The Society for Investigative Dermatology

Multilayers of InGaAs Nanostructures Grown on GaAs(210) Substrates

Multilayers of InGaAs nanostructures are grown on GaAs(210) by molecular beam epitaxy. With reducing the thickness of GaAs interlayer spacer, a transition from InGaAs quantum dashes to arrow-like nanostructures is observed by atomic force microscopy. Photoluminescence measurements reveal all the samples of different spacers with good optical properties. By adjusting the InGaAs coverage, both one-dimensional and two-dimensional lateral ordering of InGaAs/GaAs(210) nanostructures are achieved

Fibromodulin Reduces Scar Formation in Adult Cutaneous Wounds by Eliciting a Fetal-Like Phenotype

Blocking transforming growth factor (TGF)β1 signal transduction has been a central strategy for scar reduction; however, this approach appears to be minimally effective. Here, we show that fibromodulin (FMOD), a 59-kD small leucine-rich proteoglycan critical for normal collagen fibrillogenesis, significantly reduces scar formation while simultaneously increasing scar strength in both adult rodent models and porcine wounds, which simulate human cutaneous scar repair. Mechanistically, FMOD uncouples pro-migration/contraction cellular signals from pro-fibrotic signaling by selectively enhancing SMAD3-mediated signal transduction, while reducing AP-1-mediated TGFβ1 auto-induction and fibrotic extracellular matrix accumulation. Consequently, FMOD accelerates TGFβ1-responsive adult fibroblast migration, myofibroblast conversion, and function. Furthermore, our findings strongly indicate that, by delicately orchestrating TGFβ1 activities rather than indiscriminately blocking TGFβ1, FMOD elicits fetal-like cellular and molecular phenotypes in adult dermal fibroblasts in vitro and adult cutaneous wounds in vivo, which is a unique response of living system undescribed previously. Taken together, this study illuminates the signal modulating activities of FMOD beyond its structural support functions, and highlights the potential for FMOD-based therapies to be used in cutaneous wound repair. © The Author(s) 2017

Break-taking behaviour pattern of long-distance freight vehicles based on GPS trajectory data

This paper focuses on the break-taking behaviour pattern of long-distance freight vehicles, providing a new perspective on the study of behaviour patterns and simultaneously providing a reference for transport management departments and related enterprises. Based on Global Positioning System (GPS) trajectory data, we select stopping points as break-taking sites of long-distance freight vehicles and then classify the stopping points into three different classes based on the break-taking duration. We then explore the relationship of the distribution of the break-taking frequency between the three single classifications and their combinations, on the basis of the break-taking duration distribution. We find that the combination is a Gaussian distribution when each of the three individual classes is a Gaussian distribution, contrasting with the power-law distribution of the break-taking duration. Then we experimental analysis the distribution of the break-taking durations and frequencies, and find that, for the durations, the three single classifications can be fitted individually by an Exponential distribution and together by a Power-law distribution, for the frequencies, both the three single classifications and together can be fitted by a Gaussian distribution,so that can validate the above theoretical analysis. Key words: break-taking behaviour, long-distance freight vehicle, statistical analysi

Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule

Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges